tbuckley/cabot-search huggingface dataset:
Development of the oncolytic virus, CF33, and its derivatives for peritoneal-directed treatment of gastric cancer peritoneal metastases
Authors: Annie Yang, Zhifang Zhang, Shyambabu Chaurasiya, Anthony K Park, Audrey Jung, Jianming Lu, Sang-In Kim, Saul Priceman, Yuman Fong, Yanghee Woo
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Gastric cancer (GC) that metastasizes to the peritoneum is fatal. CF33 and its genetically modified derivatives show cancer selectivity and oncolytic potency against various solid tumors. CF33-hNIS and CF33-hNIS-antiPDL1 have entered phase I trials for intratumoral and intravenous treatments of unresectable solid tumors ( NCT05346484 ) and triple-negative breast cancer ( NCT05081492 ). Here, we investigated the antitumor activity of CF33-oncolytic viruses (OVs) against GC and CF33-hNIS-antiPDL1 in the intraperitoneal (IP) treatment of GC peritoneal metastases (GCPM). Methods We infected six human GC cell lines AGS, MKN-45, MKN-74, KATO III, SNU-1, and SNU-16 with CF33, CF33-GFP, or CF33-hNIS-antiPDL1 at various multiplicities of infection (0.01, 0.1, 1.0, and 10.0), and performed viral proliferation and cytotoxicity assays. We used immunofluorescence imaging and flow cytometric analysis to verify virus-encoded gene expression. We evaluated the antitumor activity of CF33-hNIS-antiPDL1 following IP treatment (3×10 5 pfu × 3 doses) in an SNU-16 human tumor xenograft model using non-invasive bioluminescence imaging. Results CF33-OVs showed dose-dependent infection, replication, and killing of both diffuse and intestinal subtypes of human GC cell lines. Immunofluorescence imaging showed virus-encoded GFP, hNIS, and anti-PD-L1 antibody scFv expression in CF33-OV-infected GC cells. We confirmed GC cell surface PD-L1 blockade by virus-encoded anti-PD-L1 scFv using flow cytometry. In the xenograft model, CF33-hNIS-antiPDL1 (IP; 3×10 5 pfu × 3 doses) treatment significantly reduced peritoneal tumors (p&lt;0.0001), decreased amount of ascites (62.5% PBS vs 25% CF33-hNIS-antiPDL1) and prolonged animal survival. At day 91, seven out of eight mice were alive in the virus-treated group versus one out of eight in the control group (p&lt;0.01). Conclusions Our results show that CF33-OVs can deliver functional proteins and demonstrate effective antitumor activity in GCPM models when delivered intraperitoneally. These preclinical results will inform the design of future peritoneal-directed therapy in GCPM patients.
Long-term follow-up of donor-derived CD7 CAR T-cell therapy in patients with T-cell acute lymphoblastic leukemia
Authors: Yue Tan, Lingling Shan, Liping Zhao, Biping Deng, Zhuojun Ling, Yanlei Zhang, Shuixiu Peng, Jinlong Xu, Jiajia Duan, Zelin Wang, Xinjian Yu, Qinlong Zheng, Xiuwen Xu, Zhenglong Tian, Yibing Zhang, Jiecheng Zhang, Alex H. Chang, Xiaoming Feng, Jing Pan
Journal: Journal of Hematology & Oncology (2023)

Donor-derived CD7-directed chimeric antigen receptor (CAR) T cells showed feasibility and early efficacy in patients with refractory or relapsed T-cell acute lymphoblastic leukemia (r/r T-ALL), in a previous phase I trial report, at a median follow-up of 6.3 months. Here we report long-term safety and activity of the therapy after a 2-year follow-up.Participants received CD7-directed CAR T cells derived from prior stem cell transplantation (SCT) donors or from HLA-matched new donors after lymphodepletion. The target dose was 1 × 106 (± 30%) CAR T cells per kg of patient weight. The primary endpoint was safety with efficacy secondary. This report focuses on the long-term follow-up and discusses them in the context of previously reported early outcomes.Twenty participants were enrolled and received infusion with CD7 CAR T cells. After a median follow-up time of 27.0 (range, 24.0-29.3) months, the overall response rate and complete response rate were 95% (19/20 patients) and 85% (17/20 patients), respectively, and 35% (7/20) of patients proceeded to SCT. Six patients experienced disease relapse with a median time-to-relapse of 6 (range, 4.0-10.9) months, and 4 of these 6 patients were found to have lost CD7 expression on tumor cells. Progression-free survival (PFS) and overall survival (OS) rates 24 months after treatment were respectively 36.8% (95% CI, 13.8-59.8%) and 42.3% (95% CI, 18.8-65.8%), with median PFS and OS of respectively 11.0 (95% CI, 6.7-12.5) months and 18.3 (95% CI, 12.5-20.8) months. Previously reported short-term adverse events (< 30 days after treatment) included grade 3-4 cytokine release syndrome (CRS; 10%) and grade 1-2 graft-versus-host disease (GVHD; 60%). Serious adverse events reported > 30 days after treatment included five infections and one grade 4 intestinal GVHD. Despite good CD7 CAR T-cell persistence, non-CAR T and natural killer cells were predominantly CD7-negative and eventually returned to normal levels in about half of the participants.In this 2-year follow-up analysis, donor-derived CD7 CAR T-cell treatment demonstrated durable efficacy in a subset of patients with r/r T-ALL. Disease relapse was the main cause of treatment failure, and severe infection was a noteworthy late-onset adverse event.ChiCTR2000034762.
Defining myocardial infarction in trials of people receiving hemodialysis: consensus report from the SONG-HD MI Expert Working group
Authors: Emma O’Lone, Fred S. Apple, James O. Burton, Fergus J. Caskey, Jonathan C. Craig, Christopher R. deFilippi, Derek Forfang, Karen A. Hicks, Vivekanand Jha, Kenneth W. Mahaffey, Patrick B. Mark, Patrick Rossignol, Nicole Scholes-Robertson, Allison Jaure, Andrea K. Viecelli, Angela Y. Wang, David C. Wheeler, David White, Wolfgang C. Winkelmayer, Charles A. Herzog
Journal: Kidney International (2023)
Prognostic value of early bone marrow MRD status in CAR-T therapy for myeloma
Authors: Radhika Bansal, Mizba Baksh, Jeremy T. Larsen, Matthew A. Hathcock, David Dingli, A. Keith Stewart, Prashant Kapoor, Taxiarchis Kourelis, Suzanne R. Hayman, Rahma M. Warsame, Rafael Fonseca, P. Leif Bergsagel, Sikander Ailawadhi, Shaji K. Kumar, Yi Lin
Journal: Blood Cancer Journal (2023)

Bone marrow (BM) assessment of minimal residual disease (MRD) is prognostic for survival in multiple myeloma (MM). BM is still hypocellular at month 1 post CAR-T, thus the value of MRD negative (MRDneg) status at this timepoint is unclear. We examined the impact of month 1 BM MRD status in MM patients who received CART at Mayo Clinic between 8/2016 and 6/2021. Among 60 patients, 78% were BM-MRDneg at month 1; and 85% (40/47) of these patients also had decreased to less than normal level of both involved and uninvolved free light chain (FLC < NL). Patients who achieved CR/sCR had higher rates of month 1 BM-MRDneg and FLC < NL. The rate of sustained BM-MRDneg was 40% (19/47). Rate of conversion from MRDpos to MRDneg was 5%(1/20). At month 1, 38%(18/47) of the BM-MRDneg were hypocellular. Recovery to normal cellularity was observed in 50%(7/14) with a median time to normalization at 12 months (range: 3-Not reached). Compared to Month 1 BM-MRDpos patients, patients who were BM-MRDneg had longer PFS irrespective of BM cellularity [PFS: 2.9 months (95% CI, 1.2-NR) vs. 17.5 months (95% CI, 10.4-NR), p < 0.0001]. Month 1 BM-MRDneg and FLC below normal were associated with prolonged survival. Our data support the continued evaluation of BM early post-CART infusion as a prognostic tool.
Engineered Living Oriented Electrospun Fibers Regulate Stem Cell Para‐Secretion and Differentiation to Promote Spinal Cord Repair (Adv. Healthcare Mater. 9/2023)
Authors: Jingzhi Xu, Kun Xi, Jincheng Tang, Juan Wang, Yunkai Tang, Liang Wu, Yichang Xu, Zonghan Xu, Liang Chen, Wenguo Cui, Yong Gu
Journal: Advanced Healthcare Materials (2023)

Electrospinning In article 2202785 by Liang Chen, Wenguo Cui, Yong Gu, and co-workers, a living-oriented fiber scaffold is found to fully exploit the advantage of stem cells, which can respond not only to regulate the local inflammatory microenvironment at the early stages of spinal cord injury, but also to further regulate the differentiation fate of stem cells, continuously release brain-derived neurotrophic factor, and promote neuronal regeneration.
Egg Microneedle for Transdermal Delivery of Active Liraglutide (Adv. Healthcare Mater. 9/2023)
Authors: Jeongyun You, Seorin Juhng, Jieun Song, Jihyun Park, Mingyu Jang, Geonwoo Kang, Huisuk Yang, Hye Su Min, Jiwoo Shin, Seri Lee, Hyuk Wan Ko, Hyungil Jung
Journal: Advanced Healthcare Materials (2023)

Transdermal Drug Delivery In article 2202473 by Hyuk Wan Ko, Hyungil Jung, and co-workers, an egg microneedle (EMN) is comprised of three main functional layers where each layers have distinct functions to enhance the drug delivery and stability. EMN allows the loaded drug to maintain the maximum drug stability, hence allowing a precise drug delivery with flexibility on drug selection. Overall, EMN is expected to provide economic and safe drug delivery platform for many transdermal delivery.
Orally Administrable Aggregation‐Induced Emission‐Based Bionic Probe for Imaging and Ameliorating Dextran Sulfate Sodium‐Induced Inflammatory Bowel Diseases (Adv. Healthcare Mater. 9/2023)
Authors: Wenyuan Wang, Ya Wu, Yihui Wang, Rui Wang, Cheng Deng, Luyang Yi, Lufang Wang, Mengrong He, Wuqi Zhou, Yuji Xie, Qiaofeng Jin, Yihan Chen, Tang Gao, Li Zhang, Mingxing Xie
Journal: Advanced Healthcare Materials (2023)

Aggregation-Induced Emission In article 2202420 by Tang Gao, Li Zhang, Mingxing Xie, and co-workers, a novel bionic probe, HBTTPIP/GPs, with an intrinsic aggregation-induced emission effect is prepared. Orally administrated HBTTPIP/GPs can be phagocytosed by intestinal macrophages, which then migrate to colonic lesions, enabling non-invasive monitoring of the severity of inflammatory bowel disease. Moreover, HBTTPIP/GPs can alleviate dextran sulfate sodium-induced colonic inflammation. Additionally, HBTTPIP/GPs can self-report the effects of treatment due to its superior macrophageimaging ability.
Target‐Catalyzed Self‐Assembly of DNA‐Streptavidin Nanogel for Enzyme‐Free miRNA Assay (Adv. Healthcare Mater. 9/2023)
Authors: Jae Chul Park, Hyebin Na, Saehan Choi, Huiju Jeon, Yoon Sung Nam
Journal: Advanced Healthcare Materials (2023)

Base-Pair Mismatch In article 2202076, Yoon Sung Nam and co-workers develop a new miRNA detection platform based on miRNA-catalyzed toehold-mediated strand displacement and the sequential formation of DNA-streptavidin nanogel. The detection limit is lowered from the nanomolar level to the picomolar level by introducing a single base-pair mismatch near the toehold enhancing strand displacement and generating a 3D nanogel network to facilitate Förster resonance energy transfer.
Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study
Authors: Gideon M. Hirschfield, Mitchell L. Shiffman, Aliya Gulamhusein, Kris V. Kowdley, John M. Vierling, Cynthia Levy, Andreas E. Kremer, Ehud Zigmond, Pietro Andreone, Stuart C. Gordon, Christopher L. Bowlus, Eric J. Lawitz, Richard J. Aspinall, Daniel S. Pratt, Karina Raikhelson, Maria S. Gonzalez-Huezo, Michael A. Heneghan, Sook-Hyang Jeong, Alma L. Ladrón de Guevara, Marlyn J. Mayo, George N. Dalekos, Joost P.H. Drenth, Ewa Janczewska, Barbara A. Leggett, Frederik Nevens, Victor Vargas, Eli Zuckerman, Christophe Corpechot, Eduardo Fassio, Holger Hinrichsen, Pietro Invernizzi, Palak J. Trivedi, Lisa Forman, David E.J. Jones, Stephen D. Ryder, Mark G. Swain, Alexandra Steinberg, Pol F. Boudes, Yun-Jung Choi, Charles A. McWherter
Journal: Hepatology (2023)

ENHANCE was a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-δ (PPAR) agonist, versus placebo in patients with primary biliary cholangitis with inadequate response or intolerance to ursodeoxycholic acid (UDCA).
A Heuristically Accelerated Reinforcement Learning-Based Neurosurgical Path Planner
Authors: Guanglin Ji, Qian Gao, Tianwei Zhang, Lin Cao, Zhenglong Sun
Journal: Cyborg and Bionic Systems (2023)

The steerable needle becomes appealing in the neurosurgery intervention procedure because of its flexibility to bypass critical regions inside the brain; with proper path planning, it can also minimize the potential damage by setting constraints and optimizing the insertion path. Recently, reinforcement learning (RL)-based path planning algorithm has shown promising results in neurosurgery, but because of the trial and error mechanism, it can be computationally expensive and insecure with low training efficiency. In this paper, we propose a heuristically accelerated deep Q network (DQN) algorithm to safely preoperatively plan a needle insertion path in a neurosurgical environment. Furthermore, a fuzzy inference system is integrated into the framework as a balance of the heuristic policy and the RL algorithm. Simulations are conducted to test the proposed method in comparison to the traditional greedy heuristic searching algorithm and DQN algorithms. Tests showed promising results of our algorithm in saving over 50 training episodes, calculating path lengths of 0.35 after normalization, which is 0.61 and 0.39 for DQN and traditional greedy heuristic searching algorithm, respectively. Moreover, the maximum curvature during planning is reduced to 0.046 from 0.139 mm-1 using the proposed algorithm compared to DQN.
Corrigendum to “Genome-wide association and Mendelian randomization study of fibroblast growth factor 21 reveals causal associations with hyperlipidemia and possibly NASH” [Metab Volume 137, December 2022, 155329]
Authors: Susanna C Larsson, Karl Michaëlsson, Marina Mola-Caminal, Jonas Höijer, Christos S Mantzoros
Journal: Metabolism (2023)
Engineered human pluripotent stem cell-derived natural killer cells with PD-L1 responsive immunological memory for enhanced immunotherapeutic efficacy
Authors: Yun Chang, Gyuhyung Jin, Weichuan Luo, Qian Luo, Juhyung Jung, Sydney N. Hummel, Sandra Torregrosa-Allen, Bennett D. Elzey, Philip S. Low, Xiaojun Lance Lian, Xiaoping Bao
Journal: Bioactive Materials (2023)

Adoptive chimeric antigen receptor (CAR)-engineered natural killer (NK) cells have shown promise in treating various cancers. However, limited immunological memory and access to sufficient numbers of allogenic donor cells have hindered their broader preclinical and clinical applications. Here, we first assess eight different CAR constructs that use an anti-PD-L1 nanobody and/or universal anti-fluorescein (FITC) single-chain variable fragment (scFv) to enhance antigen-specific proliferation and anti-tumor cytotoxicity of NK-92 cells against heterogenous solid tumors. We next genetically engineer human pluripotent stem cells (hPSCs) with optimized CARs and differentiate them into functional dual CAR-NK cells. The tumor microenvironment responsive anti-PD-L1 CAR effectively promoted hPSC-NK cell proliferation and cytotoxicity through antigen-dependent activation of phosphorylated STAT3 (pSTAT3) and pSTAT5 signaling pathways via an intracellular truncated IL-2 receptor β-chain (ΔIL-2Rβ) and STAT3-binding tyrosine-X-X-glutamine (YXXQ) motif. Anti-tumor activities of PD-L1-induced memory-like hPSC-NK cells were further boosted by administering a FITC-folate bi-specific adapter that bridges between a programmable anti-FITC CAR and folate receptor alpha-expressing breast tumor cells. Collectively, our hPSC CAR-NK engineering platform is modular and could constitute a realistic strategy to manufacture off-the-shelf CAR-NK cells with immunological memory-like phenotype for targeted immunotherapy.
Elucidating glial responses to products of diabetes-associated systemic dyshomeostasis
Authors: Dolly Ann Padovani-Claudio, Carla J. Ramos, Megan E. Capozzi, John S. Penn
Journal: Progress in Retinal and Eye Research (2023)

Diabetic retinopathy (DR) is a leading cause of blindness in working age adults. DR has non-proliferative stages, characterized in part by retinal neuroinflammation and ischemia, and proliferative stages, characterized by retinal angiogenesis. Several systemic factors, including poor glycemic control, hypertension, and hyperlipidemia, increase the risk of DR progression to vision-threatening stages. Identification of cellular or molecular targets in early DR events could allow more prompt interventions pre-empting DR progression to vision-threatening stages. Glia mediate homeostasis and repair. They contribute to immune surveillance and defense, cytokine and growth factor production and secretion, ion and neurotransmitter balance, neuroprotection, and, potentially, regeneration. Therefore, it is likely that glia orchestrate events throughout the development and progression of retinopathy. Understanding glial responses to products of diabetes-associated systemic dyshomeostasis may reveal novel insights into the pathophysiology of DR and guide the development of novel therapies for this potentially blinding condition. In this article, first, we review normal glial functions and their putative roles in the development of DR. We then describe glial transcriptome alterations in response to systemic circulating factors that are upregulated in patients with diabetes and diabetes-related comorbidities; namely glucose in hyperglycemia, angiotensin II in hypertension, and the free fatty acid palmitic acid in hyperlipidemia. Finally, we discuss potential benefits and challenges associated with studying glia as targets of DR therapeutic interventions. In vitro stimulation of glia with glucose, angiotensin II and palmitic acid suggests that: 1) astrocytes may be more responsive than other glia to these products of systemic dyshomeostasis; 2) the effects of hyperglycemia on glia are likely to be largely osmotic; 3) fatty acid accumulation may compound DR pathophysiology by promoting predominantly proinflammatory and proangiogenic transcriptional alterations of macro and microglia; and 4) cell-targeted therapies may offer safer and more effective avenues for DR treatment as they may circumvent the complication of pleiotropism in retinal cell responses. Although several molecules previously implicated in DR pathophysiology are validated in this review, some less explored molecules emerge as potential therapeutic targets. Whereas much is known regarding glial cell activation, future studies characterizing the role of glia in DR and how their activation is regulated and sustained (independently or as part of retinal cell networks) may help elucidate mechanisms of DR pathogenesis and identify novel drug targets for this blinding disease.
Bioactive superparamagnetic iron oxide-gold nanoparticles regulated by a dynamic magnetic field induce neuronal Ca2+ influx and differentiation
Authors: Elias Georgas, Muzhaozi Yuan, Jingfan Chen, Ya Wang, Yi-Xian Qin
Journal: Bioactive Materials (2023)

Treating neurodegenerative diseases, e.g., Alzheimer's Disease, remains a significant challenge due to the limited neuroregeneration rate in the brain. The objective of this study is to evaluate the hypothesis that external magnetic field (MF) stimulation of nerve growth factor functionalized superparamagnetic iron oxide-gold (NGF-SPIO-Au) nanoparticles (NPs) can induce Ca2+ influx, membrane depolarization, and enhance neuron differentiation with dynamic MF (DMF) outperforming static MF (SMF) regulation. We showed the that total intracellular Ca2+ influx of PC-12 cells was improved by 300% and 535% by the stimulation of DMF (1 Hz, 0.5 T, 30min) with NGF-SPIO-Au NPs compared to DMF alone and SMF with NGF-SPIO-Au NPs, respectively, which was attributed to successive membrane depolarization. Cellular uptake performed with the application of sodium azide proved that DMF enhanced cellular uptake of NGF-SPIO-Au NPs via endocytosis. In addition, DMF upregulated both the neural differentiation marker (β3-tubulin) and the cell adhesive molecule (integrin-β1) with the existence of NGF-SPIO-Au NPs, while SMF did not show these effects. The results imply that noninvasive DMF-stimulated NPs can regulate intracellular Ca2+ influx and enhance neuron differentiation and neuroregeneration rate.
Ambient air pollution and clinical dementia: systematic review and meta-analysis
Authors: Elissa H Wilker, Marwa Osman, Marc G Weisskopf
Journal: BMJ (2023)

Abstract Objective To investigate the role of air pollutants in risk of dementia, considering differences by study factors that could influence findings. Design Systematic review and meta-analysis. Data sources EMBASE, PubMed, Web of Science, Psycinfo, and OVID Medline from database inception through July 2022. Eligibility criteria for selecting studies Studies that included adults (≥18 years), a longitudinal follow-up, considered US Environmental Protection Agency criteria air pollutants and proxies of traffic pollution, averaged exposure over a year or more, and reported associations between ambient pollutants and clinical dementia. Two authors independently extracted data using a predefined data extraction form and assessed risk of bias using the Risk of Bias In Non-randomised Studies of Exposures (ROBINS-E) tool. A meta-analysis with Knapp-Hartung standard errors was done when at least three studies for a given pollutant used comparable approaches. Results 2080 records identified 51 studies for inclusion. Most studies were at high risk of bias, although in many cases bias was towards the null. 14 studies could be meta-analysed for particulate matter &lt;2.5 µm in diameter (PM 2.5 ). The overall hazard ratio per 2 μg/m 3 PM 2.5 was 1.04 (95% confidence interval 0.99 to 1.09). The hazard ratio among seven studies that used active case ascertainment was 1.42 (1.00 to 2.02) and among seven studies that used passive case ascertainment was 1.03 (0.98 to 1.07). The overall hazard ratio per 10 μg/m 3 nitrogen dioxide was 1.02 ((0.98 to 1.06); nine studies) and per 10 μg/m 3 nitrogen oxide was 1.05 ((0.98 to 1.13); five studies). Ozone had no clear association with dementia (hazard ratio per 5 μg/m 3 was 1.00 (0.98 to 1.05); four studies). Conclusion PM 2.5 might be a risk factor for dementia, as well as nitrogen dioxide and nitrogen oxide, although with more limited data. The meta-analysed hazard ratios are subject to limitations that require interpretation with caution. Outcome ascertainment approaches differ across studies and each exposure assessment approach likely is only a proxy for causally relevant exposure in relation to clinical dementia outcomes. Studies that evaluate critical periods of exposure and pollutants other than PM 2.5 , and studies that actively assess all participants for outcomes are needed. Nonetheless, our results can provide current best estimates for use in burden of disease and regulatory setting efforts. Systematic review registration PROSPERO CRD42021277083.